Small vessel ultrasound catheter

ABSTRACT

An ultrasound catheter adapted for accessing small vessels in the distal anatomy is disclosed. The ultrasound catheter comprises an elongate tubular body formed with a delivery lumen. The flexibility and dimensions of the tubular body allow access to the distal anatomy by advancement over the guidewire. An ultrasound radiating member is provided along the distal end portion of the tubular body for emitting ultrasound energy at a treatment site. A drug solution may also be delivered through the delivery lumen and out an exit port to the treatment site.

RELATED APPLICATIONS

[0001] The present application claims priority under 35 U.S.C. §119(e)to U.S. Provisional Application No. 60/336,660, filed Dec. 3, 2001, U.S.Provisional Application No. 60/336,627, filed Dec. 3, 2001, U.S.Provisional Application No. 60/336,571, filed Dec. 3, 2001, U.S.Provisional Application No. 60/336,630, filed Dec. 3, 2001 and U.S.Provisional Application No. 60/344,422, filed Dec. 28, 2001, each ofwhich is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

[0002] The present invention relates to a catheter having an ultrasoundassembly useful for delivering ultrasound energy at a treatment site ina body. The apparatus is particularly well suited for deliveringultrasound energy at a treatment site located within a small bloodvessel in the distal anatomy.

DESCRIPTION OF THE RELATED ART

[0003] Several therapeutic and diagnostic applications use ultrasoundenergy. For example, ultrasound energy can be used to enhance thedelivery and therapeutic effect of various therapeutic compounds. Seee.g., U.S. Pat. Nos. 4,821,740, 4,953,565 and 5,007,438. In someapplications, it is desirable to use an ultrasound catheter to deliverthe ultrasound energy and/or therapeutic compound to a specifictreatment site in the body. Such an ultrasound catheter typicallycomprises an elongate member configured for advancement through apatient's vasculature. An ultrasound assembly is mounted along thedistal end portion of the elongate member and is adapted for emittingultrasound energy. The ultrasound catheter may include a delivery lumenfor delivering the therapeutic compound to the treatment site. In thismanner, the ultrasound energy can be emitted at the treatment site toenhance the desired therapeutic effects and/or delivery of thetherapeutic compound.

[0004] In one particular application, ultrasound catheters have beensuccessfully used to treat human blood vessels that have become occludedby plaque, thrombi, emboli or other substances that reduce the bloodcarrying capacity of the vessel. See e.g., U.S. Pat. No. 6,001,069. Toremove the blockage, the ultrasound catheter is advanced through thepatient's vasculature to deliver solutions containing dissolutioncompounds directly to the blockage site. To enhance the therapeuticeffects of the dissolution compound, ultrasound energy is emitted intothe compound and/or the surrounding tissue.

[0005] In another application, ultrasound catheters may be used toperform gene therapy on an isolated region of a blood vessel or otherbody lumen. For example, as disclosed in U.S. Pat. No. 6,135,976 anultrasound catheter can be provided with one or more expandable membersfor occluding a section of the body lumen at a treatment site. A genetherapy composition is delivered to the treatment site through thedelivery lumen of the catheter. The ultrasound assembly is used to emitultrasound energy at the treatment site to enhance the entry of the genecomposition into the cells in the body lumen.

[0006] In addition to the applications discussed above, ultrasoundcatheters may be used for a wide variety of other purposes, such as, forexample, delivering and activating light activated drugs with ultrasoundenergy (see e.g., U.S. Pat. No. 6,176,842).

[0007] Over the years, numerous types of ultrasound catheters have beenproposed for various therapeutic purposes. However, none of the existingultrasound catheters is well adapted for effective use within smallblood vessels in the distal anatomy. For example, in one primaryshortcoming, the region of the catheter on which the ultrasound assemblyis located (typically along the distal end portion) is relatively rigidand therefore lacks the flexibility necessary for navigation throughdifficult regions of the distal anatomy. Furthermore, it has been foundthat it is very difficult to manufacture an ultrasound catheter having asufficiently small diameter for use in small vessels while providingadequate pushability and torqueability. Still further, it has been foundthat the distal tip of an ultrasound catheter can easily damage thefragile vessels of the distal anatomy during advancement through thepatient's vasculature.

[0008] Accordingly, an urgent need exists for an improved ultrasoundcatheter that is capable of safely and effectively navigating smallblood vessels. It is also desirable that such a device be capable ofdelivering adequate ultrasound energy to achieve the desired therapeuticpurpose. It is also desirable that such a device be capable of accessinga treatment site in fragile distal vessels in a manner that is safe forthe patient and that is not unduly cumbersome. The present inventionaddresses these needs.

SUMMARY OF THE INVENTION

[0009] There is provided in accordance with one aspect of the presentinvention, an apparatus adapted for delivering ultrasound energy withinsmall blood vessels. The apparatus comprises an elongate outer sheathhaving dimensions that allow access to the distal anatomy, including butnot limited to neurovascular and other small vessels. An elongate innercore extends through a central lumen along the entire length of thecatheter and terminates at an exit port. The inner core is provided witha delivery lumen sized for advancement over the guidewire. The deliverylumen may also be used to deliver a drug solution through the exit portto a treatment site. An ultrasound radiating member is provided alongthe distal end portion of the inner core at a location distal to theouter sheath. A sleeve may be provided over the ultrasound radiatingmember.

[0010] In one aspect, a flexible joint is provided at a locationproximal to the ultrasound radiating member to facilitate advancement ofthe catheter through a patient's vasculature. In one embodiment, theflexible joint is formed by configuring the inner core with a corrugatedregion having a reduced bending resistance. In another embodiment, theflexible joint is provided by a braided portion that is used to connectthe outer sheath with the sleeve.

[0011] In another aspect, a soft tip assembly is provided for reducingtrauma or damage to tissue along the inner wall of a blood vessel. Thesoft tip assembly may be attached to the distal end of the catheterusing a sleeve. The soft tip assembly preferably has a rounded tip.

[0012] In another aspect, the catheter is provided with a shapeable wirealong the distal end portion for pre-shaping the distal end portion ofthe catheter. Pre-shaping the distal end portion facilitates advancementover curves in the guidewire. The shapeable wire may be tapered.

[0013] In another aspect, a stiffening member is provided along the exitport at the distal tip of the catheter. The stiffening member reducesthe likelihood of “fish-mouthing” and may be used in cooperation withthe guidewire to provide a flow control valve.

[0014] In another aspect, an ultrasound radiating member is attached toor mounted on the guidewire. The guidewire is slidably received by adelivery lumen in an outer sheath for advancement of the ultrasoundradiating member to a desired treatment site. In this embodiment, thepositions of the outer sheath and the ultrasound radiating member areindependently adjustable.

[0015] In yet another aspect, an elongate tubular body is provided withan exterior surface, wherein a distal end portion of the tubular bodyhas an outer diameter of less than about 5 French for advancementthrough a small blood vessel. The tubular body defines a delivery lumenextending longitudinally therethrough and terminates at an exit port ata distal tip. A hypotube is configured to be slidably received withinthe delivery lumen and an ultrasound radiating member is coupled to adistal end portion of the hypotube. The hypotube is advanceable throughthe delivery lumen in the tubular body and out through the exit port forplacement of the ultrasound radiating member at a treatment site. A pairof wires extends longitudinally through an inner lumen in the hypotubefor providing an electrical signal to the ultrasound radiating member.

[0016] In yet another aspect, a method of treating a small blood vesselis provided. The method generally includes providing a first guidewire,an elongate tubular body, and a second guidewire having an ultrasoundradiating member disposed along a distal end. The first guidewire isadvanced through the patient's vasculature to a treatment site. Theelongate tubular body (e.g., an outer sheath) is advanced over the firstguidewire to the treatment site. The first guidewire is removed from thepatient's vasculature. The second guidewire is advanced through a lumenof the elongate tubular body such that the ultrasound radiating memberis located within a distal end portion of the elongate tubular body andultrasound energy is emitted from the ultrasound radiating member at thetreatment site.

BRIEF DESCRIPTION OF THE DRAWINGS

[0017]FIG. 1 is a side view of an ultrasound catheter that isparticularly well suited for insertion into small blood vessels of thehuman body.

[0018]FIG. 2A is a cross-sectional view of a distal end of theultrasound catheter of FIG. 1.

[0019]FIG. 2B is a cross-sectional view of the ultrasound catheter takenthrough line 2B-2B of FIG. 2A.

[0020]FIG. 3 is an alternative embodiment of the ultrasound catheterincluding a stiffener at the distal tip.

[0021]FIG. 4 is a cross-sectional view of the distal end of anultrasound catheter wherein a portion of the inner core has a corrugatedconfiguration for enhanced flexibility.

[0022]FIG. 5 is a cross-sectional view of the distal end of anultrasound catheter wherein the proximal joint comprises braidedsections for enhanced flexibility.

[0023]FIG. 6A is a cross-sectional view of the distal end of anultrasound catheter including a bendable wire adapted for providing ashapeable tip.

[0024]FIG. 6B is a cross-sectional view of the embodiment of FIG. 6Awith the shapeable tip pre-formed to facilitate advancement over aguidewire.

[0025]FIG. 7A is a top view of the distal end of an ultrasound catheterhaving a soft tip assembly.

[0026]FIG. 7B is a cross-sectional view of the soft tip assembly takenthrough line 7B-7B of FIG. 7A.

[0027]FIG. 8 is a side view an ultrasound element attached to the distalend of a guidewire.

[0028]FIG. 9 is a cross-sectional view of an ultrasound catheter usedwith the ultrasound element and guidewire of FIG. 8.

[0029]FIG. 10 is a cross-sectional view of a distal end of anothermodified embodiment of an ultrasound catheter that can be used with theultrasound element and guidewire of FIG. 8.

[0030]FIG. 11 is a side view of a distal end of a treatment wire whereinan ultrasound element is provided along the distal end of a hypotube.

[0031]FIG. 12 is a side view of a distal end of an ultrasound catheterthat incorporates the treatment wire of FIG. 11.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0032] The advancement of an ultrasound catheter through a blood vesselto a treatment site can be difficult and dangerous, particularly whenthe treatment site is located within a small vessel in the distal regionof a patient's vasculature. To reach the treatment site, it is oftennecessary to navigate a tortuous path around difficult bends and turns.During advancement through the vasculature, bending resistance along thedistal end portion of the catheter can severely limit the ability of thecatheter to make the necessary turns. Moreover, as the catheter isadvanced, the distal tip of the catheter is often in contact with theinner wall of the blood vessel. The stiffness and rigidity of the distaltip of the catheter may lead to significant trauma or damage to thetissue along the inner wall of the blood vessel. As a result,advancement of an ultrasound catheter through small blood vessels can beextremely hazardous. Therefore, a need exists for an improved ultrasoundcatheter design that allows a physician to more easily navigatedifficult turns in small blood vessels while minimizing trauma and/ordamage along the inner walls of the blood vessels.

[0033] To address this need, preferred embodiments of the presentinvention described herein provide an ultrasound catheter that is wellsuited for use in the treatment of small blood vessels or other bodylumens having a small inner diameter. The ultrasound catheter can beused to enhance the therapeutic effects of drugs, medication and otherpharmacological agents at a treatment site within the body. See e.g.,U.S. Pat. Nos. 5,318,014, 5,362,309, 5,474,531, 5,628,728, 6,001,069,and 6,210,356. Certain preferred embodiments of the ultrasound catheterare particularly well suited for use in the treatment of thromboticocclusions in small blood vessels, such as, for example, the cerebralarteries. In addition, preferred embodiments may also find utility inother therapeutic applications, such as, for example, performing genetherapy (see e.g., U.S. Pat. No. 6,135,976), activating light activateddrugs for producing targeted tissue death (see e.g., U.S. Pat. No.6,176,842) and causing cavitation to produce various desirablebiological effects (see e.g., U.S. Pat. No. RE36,939). Moreover, suchtherapeutic applications may be used in wide variety of locations withinthe body, such as, for example, in other parts of the circulatorysystem, solid tissues, duct systems and body cavities. It is alsoanticipated that the ultrasound catheters disclosed herein, andvariations thereof, may find utility in other medical applications, suchas, for example, diagnostic and imaging applications.

[0034] Ultrasound catheters and methods disclosed herein, and similarvariations thereof, may also be useful for applications wherein theultrasound energy provides a therapeutic effect by itself. For example,ultrasound energy may be effective for uses such as preventing and/orreducing stenosis and/or restenosis, tissue ablation, abrasion ordisruption, promoting temporary or permanent physiological changes inintracellular or intercellular structures, or rupturing micro-balloonsor micro-bubbles for drug delivery. See e.g., U.S. Pat. Nos. 5,269,291and 5,431,663. In addition, the methods and devices disclosed herein mayalso find utility in applications that do not require the use of acatheter. For example the methods and devices may be used for enhancinghyperthermic drug treatment or using an external ultrasound source toenhance the therapeutic effects of drugs, medication and otherpharmacological agents at a specific site within the body or to providea therapuetic or diagnostic effect by itself. See e.g., U.S. Pat. Nos.4,821,740, 4,953,565, 5,007,438 and 6,096,000. The entire disclosure ofeach of the above-mentioned patents is hereby incorporated by referenceherein and made a part of this specification.

[0035] As used herein, the term “ultrasound energy” is a broad term andis used in its ordinary sense and means, without limitation, mechanicalenergy transferred through pressure or compression waves with afrequency greater than about 20 KHz. In one embodiment, the waves of theultrasound energy have a frequency between about 500 KHz and 20 MHz andin another embodiment between about 1 MHz and 3 MHz. In yet anotherembodiment, the waves of the ultrasound energy have a frequency of about3 MHz.

[0036] As used herein, the term “catheter” is a broad term and is usedin its ordinary sense and means, without limitation, an elongateflexible tube configured to be inserted into the body of a patient, suchas, for example, a body cavity, duct or vessel.

[0037] Preferred Features of Ultrasound Catheter

[0038] Referring now to FIGS. 1 through 2B, for purposes ofillustration, preferred embodiments of the present invention provide anultrasound catheter 100 that is particularly well suited for use withinsmall vessels of the distal anatomy, such as, for example, in theremote, small diameter, neurovasculature in the brain.

[0039] As shown in FIGS. 1 and 2A, the ultrasound catheter 100 generallycomprises a multi-component tubular body 102 having a proximal end 104and a distal end 106. The tubular body 102 and other components of thecatheter 100 can be manufactured in accordance with any of a variety oftechniques well know in the catheter manufacturing field. As discussedin more detail below, suitable material dimensions can be readilyselected taking into account the natural and anatomical dimensions ofthe treatment site and of the desired percutaneous access site.

[0040] Preferably, the tubular body 102 can be divided into at leastthree sections of varying stiffness. The first section, which preferablyincludes the proximal end 104, is generally more stiff than a secondsection, which lies between the proximal end 104 and the distal end 106of the catheter. This arrangement facilitates the movement and placementof the catheter 102 within small vessels. The third section, whichincludes ultrasound radiating element 124, is generally stiffer than thesecond section due to the presence of the ultrasound radiating element124.

[0041] In each of the embodiments described herein, the assembledultrasound catheter preferably has sufficient structural integrity, or“pushability,” to permit the catheter to be advanced through a patient'svasculature to a treatment site without buckling or kinking. Inaddition, the catheter has the ability to transmit torque, such that thedistal portion can be rotated into a desired orientation after insertioninto a patient by applying torque to the proximal end.

[0042] The elongate flexible tubular body 102 comprises an outer sheath108 (see FIG. 2A) that is positioned upon an inner core 110. In anembodiment particularly well suited for small vessels, the outer sheath108 comprises extruded PEBAX, PTFE, PEEK, PE, polymides, braidedpolymides and/or other similar materials. The distal end portion of theouter sheath 108 is adapted for advancement through vessels having avery small diameter, such as those in the neurovasculature of the brain.Preferably, the distal end portion of the outer sheath 108 has an outerdiameter between about 2 and 5 French. More preferably, the distal endportion of the outer sheath 108 has an outer diameter of about 2.8French. In one preferred embodiment, the outer sheath 108 has an axiallength of approximately 150 centimeters.

[0043] In other embodiments, the outer sheath 108 can be formed from abraided tubing formed of, by way of example, high or low densitypolyethylenes, urethanes, nylons, etc. Such an embodiment enhances theflexibility of the tubular body 102. For enhanced pushability andtorqueability, the outer sheath 108 may be formed with a variablestiffness from the proximal to the distal end. To achieve this, astiffening member may be included along the proximal end of the tubularbody 102.

[0044] The inner core 110 defines, at least in part, a delivery lumen112, which preferably extends longitudinally along the entire length ofthe catheter 100. The delivery lumen 112 has a distal exit port 114 anda proximal axis port 116. Referring again to FIG. 1, the proximal accessport 116 is defined by drug inlet port 117 of a back end hub 118, whichis attached to the proximal end 104 of the other sheath 108. Theillustrated back end hub 118 is preferably attached to a control boxconnector 120, the utility of which will be described in more detailbelow.

[0045] The delivery lumen 112 is preferably configured to receive aguide wire (not shown). Preferably, the guidewire has a diameter ofapproximately 0.008 to 0.012 inches. More preferably, the guidewire hasa diameter of about 0.010 inches. The inner core 110 is preferablyformed from polymide or a similar material which, in some embodiments,can be braided to increase the flexibility of the tubular body 102.

[0046] With particular reference to FIGS. 2A and 2B, the distal end 106of the catheter 102 preferably includes the ultrasound radiating element124. In the illustrated embodiment, the ultrasound radiating element 124comprises an ultrasound transducer, which converts, for example,electrical energy into ultrasound energy. In a modified embodiment, theultrasound energy can be generated by an ultrasound transducer that isremote from the ultrasound radiating element 124 and the ultrasoundenergy can be transmitted via, for example, a wire to the ultrasoundradiating element 124.

[0047] In the embodiment illustrated in FIGS. 2A and 2B, the ultrasoundradiating element 124 is configured as a hollow cylinder. As such, theinner core 110 can extend through the lumen of the ultrasound radiatingelement 124. The ultrasound radiating element 124 can be secured to theinner core 110 in any suitable manner, such as with an adhesive. Apotting material may also be used to further secure the mounting of theultrasound radiating element along the central core.

[0048] In other embodiments, the ultrasound radiating element 124 can beconfigured with a different shape without departing from the scope ofthe invention. For example, the ultrasound radiating element may takethe form of a solid rod, a disk, a solid rectangle or a thin block.Still further, the ultrasound radiating element 124 may comprise aplurality of smaller ultrasound radiating elements. The illustratedarrangement is the generally preferred configuration because it providesfor enhanced cooling of the ultrasound radiating element 124. Forexample, in one preferred embodiment, a drug solution can be deliveredthrough the delivery lumen 112. As the drug solution passes through thelumen of the ultrasound radiating element, the drug solution mayadvantageously provide a heat sink for removing excess heat generated bythe ultrasound radiating element 124. In another embodiment, a returnpath can be formed in the space 138 between the outer sheath and theinner core such that coolant from a coolant system can be directedthrough the space 138.

[0049] The ultrasound radiating element 40 is preferably selected toproduce ultrasound energy in a frequency range that is well suited forthe particular application. Suitable frequencies of ultrasound energyfor the applications described herein include, but are not limited to,from about 20 KHz to about 20 MHz. In one embodiment, the frequency isbetween about 500 KHz and 20 MHz and in another embodiment from about 1MHz and about 3 MHz. In yet another embodiment, the ultrasound energyhas a frequency of about 3 MHz.

[0050] As mentioned above, in the illustrated embodiment, ultrasoundenergy is generated from electrical power supplied to the ultrasoundradiating element 124. The electrical power can be supplied through thecontroller box connector 120, which is connected to a pair wires 126,128 that extend through the catheter body 102. The electrical wires 126,128 can be secured to the inner core 110, lay along the inner core 110and/or extend freely in the space between the inner core 110 and theouter sheath 108. In the illustrated arrangement, the first wire 126 isconnected to the hollow center of the ultrasound radiating element 124while the second wire 128 is connected to the outer periphery of theultrasound radiating element 124. The ultrasound radiating element 124is preferably, but is not limited to, a transducer formed of apiezolectic ceramic oscillator or a similar material.

[0051] With continued reference to FIGS. 2A and 2B, the distal end 104of the catheter 100 preferably includes a sleeve 130, which is generallypositioned about the ultrasound radiating element 124. The sleeve 130 ispreferably constructed from a material that readily transmits ultrasoundenergy. Suitable materials for the sleeve 130 include, but are notlimited to, polyolefins, polyimides, polyester and other materialshaving a relatively low impedance to ultrasound energy. Low ultrasoundimpedance materials are materials that readily transmit ultrasoundenergy with minimal absorption of the ultrasound energy. The proximalend of the sleeve 130 can be attached to the outer sheath 108 with anadhesive 132. To improve the bonding of the adhesive 132 to the outersheath 108, a shoulder 127 or notch may be formed in the outer sheathfor attachment of the adhesive thereto. Preferably, the outer sheath 108and the sleeve 130 have substantially the same outer diameter.

[0052] In a similar manner, the distal end of the sleeve 130 can beattached to a tip 134. In the illustrated arrangement, the tip 134 isalso attached to the distal end of the inner core 110. Preferably, thetip is between about 0.5 and 4.0 millimeters in length. More preferably,the tip is about 2.0 millimeters in length. As illustrated, the tip ispreferably rounded in shape to reduce trauma or damage to tissue alongthe inner wall of a blood vessel or other body structure duringadvancement toward a treatment site.

[0053] With continued reference to FIG. 2B, the catheter 100 preferablyincludes at least one temperature sensor 136 along the distal end 106.The temperature sensor 136 is preferably located on or near theultrasound radiating element 124. Suitable temperature sensors includebut are not limited to, diodes, thermistors, thermocouples, resistancetemperature detectors (RTDs), and fiber optic temperature sensors thatused thermalchromic liquid crystals. The temperature sensor ispreferably operatively connected to a control box (not shown) through acontrol wire, which extends through the catheter body 102 and back endhub 118 and is operatively connected to a control box through thecontrol box connector 120. The control box preferably includes afeedback control system having the ability to monitor and control thepower, voltage, current and phase supplied to the ultrasound radiatingelement. In this manner, the temperature along the relevant region ofthe catheter can be monitored and controlled for optimal performance.Details of the control box can be found in Assignee's copendingprovisional application entitled CONTROL POD FOR ULTRASONIC CATHETER,Application Serial No. 60/336,630, filed Dec. 3, 2001, which isincorporated by reference in its entirety.

[0054] In one exemplary application of the ultrasound catheter 100described above, the apparatus may be used to remove a thromboticocclusion from a small blood vessel. In one preferred method of use, afree end of a guidewire is percutaneously inserted into the patient'svasculature at a suitable first puncture site. The guidewire is advancedthrough the vasculature toward a treatment site wherein the blood vesselis occluded by the thrombus. The guidewire wire is preferably thendirected through the thrombus.

[0055] After advancing the guidewire to the treatment site, the catheter100 is thereafter percutaneously inserted into the vasculature throughthe first puncture site and is advanced along the guidewire towards thetreatment site using traditional over-the-guidewire techniques. Thecatheter 100 is advanced until the distal end 106 of the catheter 100 ispositioned at or within the occlusion. The distal end 106 of thecatheter 100 may include one or more radiopaque markers (not shown) toaid in positioning the distal end 106 within the treatment site.

[0056] After placing the catheter, the guidewire can then be withdrawnfrom the delivery lumen 112. A drug solution source (not shown), such asa syringe with a Luer fitting, is attached to the drug inlet port 117and the controller box connector 120 is connected to the control box. Assuch, the drug solution can be delivered through the delivery lumen 112and out the distal access port 114 to the thrombus. Suitable drugsolutions for treating a thrombus include, but are not limited to, anaqueous solution containing Heparin, Uronkinase, Streptokinase, and/ortissue Plasminogen Activator (TPA).

[0057] The ultrasound radiating element 124 is activated to emitultrasound energy from the distal end 106 of the catheter 100. Asmentioned above, suitable frequencies for the ultrasound radiatingelement 124 include, but are not limited to, from about 20 KHz to about20 MHz. In one embodiment, the frequency is between about 500 KHz and 20MHz and in another embodiment between about 1 MHz and 3 MHz. In yetanother embodiment, the ultrasound energy is emitted at a frequency ofabout 3 MHz. The drug solution and ultrasound energy are applied untilthe thrombus is partially or entirely dissolved. Once the thrombus hasbeen dissolved to the desired degree, the catheter 100 is withdrawn fromthe treatment site.

[0058] Stiffening Component

[0059] Referring again to FIG. 2A, because the diameter of the distalexit port 114 is often relatively large compared with the diameter ofthe guidewire (not shown), a gap may exist between the inner rim of thetip 134 and the guidewire. If sufficiently large, this gap may cause thetip 134 of the catheter to catch or snag on an object along the exitport 114. If the tip 134 catches on an object, the exit port 114 maystretch (i.e., increase in diameter) as the catheter is pushed forward.This effect is particularly likely to occur at vessel bifurcations andwill hereinafter be referred to as “fish-mouthing.”

[0060]FIG. 3 illustrates an embodiment adapted to reduce the likelihoodof fish-mouthing wherein a circular stiffening component 140 is providedalong the distal tip 134. The circular stiffening component 140 reducesthe gap between the tip 134 and the guidewire, and is preferably made ofa stiff material, such as, for example, aluminum, that will prevent thetip 134 from fish-mouthing. Additionally, if the guidewire is formedwith a variable diameter, cooperation of the guidewire and the circularstiffening component 140 may be advantageously used as a valve. Byadjusting the relative positions of the guidewire and catheter, it ispossible to control the delivery of drugs, medications, or othertherapeutic compounds through the exit port 114 along the tip 134. Asseen in FIG. 3, this embodiment also includes a variation of the innercore 110A having a flared end that may be inserted into acircumferential notch 142 formed in the distal tip 134. Insertion of theflared end into the circumferential notch provides for enhancedstructural integrity.

[0061] In alternative embodiments, fish-mouthing may be prevented byincreasing the thickness of the tip 134, or by manufacturing the tip 134using a material with increased stiffness. In such embodiments, the tip134 will have decreased flexibility, and therefore will be lesssusceptible to fish-mouthing.

[0062] Flexible Joint

[0063] Referring again to FIG. 2A, in modified embodiments of thepresent invention, the rigidity of the catheter along the joint(hereinafter referred to as the “proximal element joint”) between theouter sheath 108 and sleeve 130 may be reduced significantly. Therigidity of the proximal element joint is reduced to further enhanceflexibility, prevent kinking of the flexible support section of thecatheter, and to facilitate tracking of the catheter over the guidewire.

[0064] In such embodiments, the used of an adhesive may be eliminated,and the proximal end of the sleeve 130 may be attached to the outersheath 108 at the proximal element joint using a direct bonding methodadapted to create a more flexible proximal element joint. Examples ofsuch direct bonding methods include, but are not limited to, the use ofheat, a solvent, a mold, or a cast. Alternatively, a reflow, or “diewiping” technique may be employed wherein an extruded catheter shaft iscovered with a heat shrink tube and heated to reflow and bond thepolymers within the catheter shaft. An external heat source may beemployed in a reflow technique, or if the catheter includes metalcomponents at the proximal element joint, radio frequency (“RF”) energymay be used to heat and bond the polymers within the catheter shaft.

[0065]FIG. 4 illustrates yet another alternative embodiment for reducingthe rigidity of the proximal element joint to thereby enhance theflexibility of the ultrasound catheter. As illustrated in FIG. 4, theinner core 410 includes a corrugated portion 452 along the proximalelement joint just proximal of the ultrasound radiating element 424. Insuch embodiments, a Teflon® liner 450 may be adapted to surround theinner surface of the corrugated portion 452 of the inner core 410 toprevent the guidewire from catching on the corrugations. Additionally, aflexible filler material 456 and a flexible cover sleeve 454 may beadapted to cover the exterior surface of the corrugated portion 452 ofthe catheter to prevent the catheter from catching on the interior wallsof the vessel anatomy. A corrugated portion 452 of the inner core 410may be created by placing a close-fitting pin within a portion of thepolyimide material used to form the inner core, and applying acompressive force to the polyimide material on either side of the pin.When the pin is removed from the inner core 410, the corrugated portion452 of the inner core 410 will have enhanced flexibility and willthereby increase the flexibility of the ultrasound catheter.

[0066] In still other embodiments, the rigidity of the proximal elementjoint may be further reduced by forming the inner core 410 of thedelivery lumen 412 of a material with increased flexibility andresistance to kinking. For example, the inner core 410 of the deliverylumen 412 may comprise a Teflon®-lined polyimide shaft. Additionally, acoil or braid may be incorporated into the delivery lumen 412, therebyfurther reducing susceptibility to kinking without increasing therigidity of the catheter.

[0067]FIG. 5 illustrates yet another alternative embodiment wherein therigidity of the proximal element joint 548 is reduced by providing aouter sheath 508 that includes an embedded braid 560. Furthermore, theouter sheath 508 is attached to the sleeve 530 using a flexible exposedbraided portion 558. A flexible filler material 556 and a flexible coversleeve 554 are used to bond the outer sheath 508, the sleeve 530 and theexposed braided portion 558 together. This embodiment provides thecatheter with a flexible region just proximal to the ultrasoundradiating member 524. In various preferred embodiments, the braidedsections may be formed of high or low density polyethylenes, urethanesor nylons.

[0068] Shapeable Tip

[0069]FIG. 6A illustrates yet another modified embodiment wherein theultrasound catheter provides improved tracking over the guidewire 602.Prolapsing of a guidewire is most likely to occur at small vessel radii,where the guidewire 602 follows a sharp turn, and where the angle θformed by the intersection between the guidewire 602 and the catheterbody is large. In order to reduce the incident angle θ between theguidewire and catheter body, a tapered wire 642 is provided along theexterior of the outer sheath 608 for shaping the distal end of thecatheter. The tapered wire 642 may be set in a flexible potting orfiller material 644, which is contained within a flexible sleeve 646.The tapered wire 642 is preferably comprised of a pliable material, suchthat it may be pre-formed into a selectable desired orientation beforeuse. Pre-forming of the tapered wire 642 assists the physician insteering the catheter to follow the guidewire 602 reliably around smallvessel radii by reducing the angle θ formed by the intersection betweenthe guidewire 602 and the catheter body. The tapered wire is preferablyprovided in the region surrounding the ultrasound radiating element 624.FIG. 6B illustrates the embodiment of FIG. 6A in use with the tippre-formed for improved tracking over the guidewire.

[0070] Soft Tip Assembly

[0071] In addition to having excellent flexibility, it is also desirablefor an ultrasound catheter to have a rounded and/or soft tip assemblyfor minimizing trauma or damage to the tissue along the inner wall ofthe blood vessel. This feature is particularly important duringadvancement through small blood vessels in the neurovasculature.

[0072]FIG. 7A illustrates an alternative embodiment wherein the distalend portion of an ultrasound catheter is provided with a soft tipassembly 700. In the illustrated embodiment, the ultrasound cathetergenerally comprises an elongate shaft body 702, an ultrasound radiatingelement 704, an elongate soft tip 706 and a connecting sleeve 708. Thesoft tip 706 of the catheter is constructed to be softer and moreflexible than the shaft body 702 for the purpose of minimizing oreliminating damage to the tissue along the inner wall of a blood vessel.In the illustrated embodiment, the soft tip 706 is configured as asubstantially hollow member including a delivery lumen 710. The lumen710 may be used for receiving a guidewire and/or for delivering drugs toa treatment site. Preferably, the shaft body 702 and the soft tip 706have substantially the same outer diameter. The delivery lumen 710terminates at an exit port 720 at the extreme distal tip of the soft tipassembly.

[0073] Still referring to FIG. 7A, the ultrasound radiating element 704is provided at a location just distal to the shaft body 702 and justproximal of the soft tip 710. Preferably, a small gap 712 is providedbetween the ultrasound radiating element 704 and the elongate body 702and also between the ultrasound radiating element 704 and the soft tip706. In the illustrated embodiment, a single cylindrical ultrasoundradiating element 704 is provided, however, in alternative embodiments,others variations may be used, such as, for example a plurality ofsmaller ultrasound radiating elements.

[0074] In the illustrated embodiment, the shaft body 702, ultrasoundradiating element 704 and soft tip 706 are secured together by thesleeve 708. The ultrasound radiating element 704 is contained within thelumen of the sleeve 708. The proximal end 714 of the sleeve 708 extendsover the distal portion of the shaft body 702. The distal end 716 of thesleeve 708 extends over the proximal end of the soft tip 706. In oneembodiment, the sleeve 708 is formed of heat shrink tubing. To maximizeeffectiveness of the ultrasound catheter, the sleeve 708 is preferablyconstructed of a material having a low impedance to ultrasound energy.FIG. 7B illustrates a cross-sectional view of the soft tip assembly ofFIG. 7A as seen through line 7B-7B.

[0075] Referring again to FIG. 7A, the illustrated embodiment of thesoft tip assembly 706 is formed with a plurality of side holes 718. Theside holes 718 are in communication with the delivery lumen 710 and areprovided for enhancing the delivery of drugs to the treatment site.Using the side holes 718, the therapeutic agent can be deliveredradially at a location closer to the ultrasound radiating element 704.The illustrated embodiment includes two side holes, however, inalternative embodiments, any number of side holes may be used withoutdeparting form the spirit and scope of the invention. Alternatively, thesoft tip assembly may be configured without any side holes.

[0076] In alternative embodiments, the soft tip assembly may have asolid tip wherein drugs exit the tip assembly only through side ports.In the embodiments with a solid tip, the guidewire exits the catheterthrough a side port, such as in a rapid exchange or monorail catheterdesign. In another embodiment, the soft tip assembly includes aradiopaque material to provide for high visibility under fluoroscopy. Invarious alternative embodiments, the soft tip assembly may have avariety of different lengths, such as, for example, 1 mm, 3 mm and 6 mm.

[0077] In operation, the ultrasound catheter is advanced over aguidewire that extends through the delivery lumen 710. As the ultrasoundcatheter is advanced through a small blood vessel, the soft tip assemblybends and conforms to the shape of the blood vessel to reduce thepressure applied along the inner wall. The rounded tip of the soft tipassembly also minimizes trauma to the tissue as it is advanced along theinner walls of the blood vessels. The soft tip assembly can bend tofacilitate the advancement of the catheter, yet will return tosubstantially its original shape. After the ultrasound element ispositioned in the desired location, the guidewire may be removed and thedelivery lumen 710 used for the delivery of a therapeutic agent to thetreatment site.

[0078] The soft tip assembly is preferably made of a soft polymerextrusion, such as, for example, polyimide. In one preferred method ofconstruction, the soft tip assembly is constructed by first cutting theextruded soft tubular body into a length of approximately 3 to 6 mm. Thedistal tip is then rounded and smoothed using a heated die with thedesired contour. In the embodiments wherein side holes are provided, theside holes are created using a 0.010 inch hole plunger. The soft tipassembly is then attached to the elongate shaft body using an adhesiveor by thermal bonding. Alternatively, a length of heat shrink tubing maybe used to secure the shaft body to the soft tip assembly.

[0079] Ultrasound Element on a Guidewire

[0080]FIGS. 8 and 9 illustrate another modified embodiment of anultrasound catheter 850. As shown in FIG. 8, in this embodiment, anultrasound radiating element 852 is connected to or mounted on a distalend 854 of a guidewire 856. In the illustrated arrangement, theultrasound radiating element 852 is in the shape of a hollow cylinder.As such, the guidewire 856 can extend through the ultrasound radiatingelement 852, which is positioned over the guidewire 856. The ultrasoundradiating element 852 can be secured to the guidewire 856 in anysuitable manner, such as with an adhesive. In other embodiments, theultrasound radiating element 856 can be of a different shape, such as,for example, a solid cylinder, a disk, a solid rectangle or a plateattached to the guidewire 856. The ultrasound radiating element 852 canalso be formed from a plurality of smaller ultrasound elements.

[0081] In the illustrated embodiment, ultrasound energy is generatedfrom electrical power supplied to the ultrasound radiating element 852.As such, the ultrasound radiating element 852 is connected to a pair ofwires 860, 862 that can extend through the catheter body. In theillustrated embodiment, the wires 860, 862 are preferably secured to theguidewire 856 with the first wire 860 is connected to the hollow centerof the ultrasound radiating element 852 and the second wire 862connected to the outer periphery of the ultrasound radiating element852. As with the previous embodiments, the ultrasound radiating element852 is preferably formed from, but is not limited to, a piezolecticceramic oscillator or a similar material. Other wiring schemes includewires connected to both ends of a solid transducer or both sides of ablock. The ultrasound radiating element 852 and the wires 860, 862 arepreferably covered with a thin insulating material 857.

[0082]FIG. 9 illustrates one embodiment of a catheter 850 that can beused with the guidewire 856 described above. In this embodiment, thecatheter 850 includes an outer sheath 866, which defines the deliverylumen 868. As such, the illustrated embodiment does not include an innercore. The delivery lumen 868 includes a distal opening 870. As will beexplained below, in one arrangement, the distal opening 870 can beconfigured such that the guidewire 856 and the ultrasound radiatingelement 852 can be withdrawn into the catheter 850 through the distalopening 870. In such an arrangement, a distal end 872 of the catheter850 preferably includes a sleeve 874, that is constructed from amaterial that readily transmits ultrasound energy as described above. Inanother arrangement, the distal opening 870 can be configured such thatultrasound radiating element 852 can not be withdrawn into the catheter850 through the distal opening 870. In such an arrangement, theultrasound radiating element 852 is configured to operate outside thecatheter 850 near the distal opening 870.

[0083] In one embodiment, the distal end 854 of the guidewire 856 ispercutaneously inserted into the arterial system at a suitable firstpuncture site. The guidewire 856 and the ultrasound radiating element852 are advanced through the vessels towards a treatment site, whichincludes a thrombotic occlusion. The guidewire 856 is preferably thendirected through the thrombotic occlusion.

[0084] The catheter 850 is thereafter percutaneously inserted into thefirst puncture site and advanced along the guidewire 856 towards thetreatment site using traditional over-the-guidewire techniques. Thecatheter 850 is advanced until the distal end of the catheter 856 ispositioned at or within the occlusion. Preferably, the distal endincludes radio opaque markers to aid positioning the distal end withinthe treatment site.

[0085] In one embodiment, the guidewire 856 can then be withdrawn untilthe ultrasound radiating element 852 is positioned within the distal end874 of the catheter 850. In such an arrangement, the catheter 850 caninclude a proximal stop 875 to aid the positioning of the ultrasoundradiating element 852. In another embodiment, the guidewire can bewithdrawn until the ultrasound radiating element 852 is located near oradjacent the distal opening 870. The catheter 850 can then be operatedas described above.

[0086] In another modified embodiment, a standard guidewire (not shown)is percutaneously inserted into the first puncture site and advancedthrough the vessels towards and preferably through the occlusion. Thecatheter 850 is thereafter percutaneously inserted into the firstpuncture site and advanced along the standard guidewire towards thetreatment site using traditional over-the-guidewire techniques. Thecatheter 850 preferably is advanced until the distal end of the catheter850 is positioned at or within the occlusion. The standard guidewire canthen be withdrawn from the delivery lumen. The guidewire 856 andultrasound radiating element 852 of FIG. 8 can then be inserted into thedelivery lumen. In one embodiment, the ultrasound radiating element 852is advanced until it is positioned in the distal end of the catheter850. In another embodiment, the ultrasound radiating element 852 isadvanced until it exits the distal end 870 of the delivery lumen 868.The catheter can then be operated as describe above.

[0087]FIG. 10 illustrates yet another modified embodiment of anultrasound catheter 1000 that can be used with the guidewire 1056 andultrasound radiating element 1052, as described above. In thisembodiment, the guidewire lumen 1068 is defined by an inner sleeve ortube 1002. The distal end 1070 of the delivery lumen 1068 can beconfigured as described above for preventing or withdrawing theultrasound radiating element 1052 into catheter 1050. In the illustratedarrangement, the delivery lumen 1068 can be used to transport the drugsolution. In another arrangement, the space 1004 between the inner core1002 and the outer sheath 1066 can be used to transport the drugsolution. In such an arrangement, the outer sheath 1066 preferablyincludes one or more holes positioned at the distal end 1072 of theouter sheath 1066. The catheter can be advanced on the guidewire 856 ofFIG. 8 or a standard guidewire as described above.

[0088] Ultrasound Element on a Hyoptube

[0089]FIGS. 11 and 12 illustrate yet another embodiment of an ultrasoundcatheter 1101 that is particularly well suited for use with smallvessels of the distal anatomy. As shown in FIG. 12, this embodiment ofthe ultrasound catheter 1101 generally comprises a treatment wire 1103and a microcatheter 1105.

[0090]FIG. 11 illustrates a preferred embodiment of a treatment wire1103. As shown in FIG. 11, in this embodiment, an ultrasound radiatingelement 1106 is connected to the distal tip of a hypotube 1108. Asdiscussed with reference to the small vessel catheters described above,the ultrasound radiating element can take many shapes and forms. Theultrasound radiating element 1106 is potted in an insulating materialeither as a conformal coating or potted inside an outer sleeve. Thepotting 1110 over the ultrasound radiating element 1106 sections isoptimized for transmission of ultrasound energy. In the embodimentillustrated in FIG. 11, the width of the potted ultrasound radiatingelement 1112 is approximately 0.018 inches. An epoxy or similar adhesiveknown in the catheter manufacturing field connects the potted ultrasoundradiating element 1112 with the hypotube 1108 at junction 1114.

[0091] The hypotube 1108 is made from Nitinol or stainless steel orother suitable material in accordance with the techniques and materialsknown in the catheter manufacturing field. In one embodiment, thehypotube has a diameter of approximately 0.014 to 0.015 inches. Thehypotube 1108 provides an insulated lumen 1116 through which one can runpower wires 1118 for the ultrasound radiating element 1106 or wires fortemperature sensors (not shown) in the microcatheter 1105. Themicrocatheter 1105, into which the treatment wire 1103 is inserted, hasa diameter greater than the width of the potted ultrasound radiatingelement 1112.

[0092] As shown in FIG. 11, in this embodiment, a flexible nose 1120 isconnected to the distal end of the potted ultrasound radiating element1112. An epoxy or similar adhesive known in the catheter manufacturingfield connects the flexible nose 1120 to the potted ultrasound radiatingelement 1112 at junction 1122. The flexible nose 1120 is at leastapproximately 3 millimeters in length and functions as a guidewire whenthe treatment wire 1103 is inserted into a microcatheter 1105. In theembodiment illustrated in FIG. 11, the flexible nose 1120 is a soft coilmade of metal or another suitable material known in the art. Theflexible nose 1120 facilitates the delivery of the potted ultrasoundradiating element 1112 through the microcatheter 1105 and into thevessel lumen of the treatment site. Preferably, the flexible nose 1120is tapered in a manner so that the distal end of the nose has a smallerdiameter than the proximal end.

[0093] In use, a free end of a guidewire is percutaneously inserted intothe arterial system at a suitable first puncture site. The guidewire isadvanced through the vessels toward a treatment site, such as, forexample, a thrombotic occlusion in the middle cerebral artery.

[0094] The microcatheter 1105 is thereafter percutaneously inserted intothe first puncture site and advanced along the guidewire towards thetreatment site using traditional over-the-guidewire techniques. Thecatheter 1105 is advanced until the distal end 1199 of the catheter 1105is positioned at or within the occlusion. Preferably, the distal end1199 includes radio opaque markers to aid positioning the distal end1199 within the treatment site.

[0095] The guidewire can then be withdrawn from the delivery lumen 1197of the microcatheter 1105. As illustrated in FIG. 12, the treatment wire1103 is then inserted and advanced through the microcatheter 1105 to thetreatment site. The potted ultrasound radiating element 1112 of thetreatment wire 1103 is advanced beyond the distal end 1199 of themicrocatheter and into lumen of the vessel. Once at the target site, theultrasound radiating element 1106 provides ultrasound energy.

[0096] Preferably, drugs 1124, including but not limited to drugs havingthrombolytic effects, are infused through the microcatheter 1105 anddelivered into the vessel around the ultrasound radiating element 1106at the same time the ultrasound radiating element 1106 emits energy. Itis believed that the transmission of ultrasound energy at the treatmentsite enhances drug uptake and activity and has other therapeuticeffects. Preferably, the potted ultrasound radiating element 1112extends far enough away from the distal tip 1199 of the microcatheter1105 to facilitate the infusion of drugs (shown by arrow 1124) throughthe microcatheter 1105 and into the vessel.

[0097] While the foregoing detailed description has described severalembodiments of the apparatus and methods of the present invention, it isto be understood that the above description is illustrative only and isnot limiting of the disclosed invention. It will be appreciated that thespecific dimensions and configurations can differ from those describedabove, and that the methods described can be used within any biologicalconduit within the body and remain within the scope of the presentinvention. Thus, the invention is to be limited only by the claims thatfollow.

We claim:
 1. A catheter, comprising: an elongate outer sheath with anexterior surface, wherein a distal end portion of said outer sheath hasan outer diameter of less than about 5 French for advancement through asmall blood vessel, said outer sheath defining a central lumen extendinglongitudinally therethrough; an elongate inner core extending throughsaid central lumen of said outer sheath and terminating at an exit portlocated at a distal tip, said inner core defining a delivery lumenadapted for delivery of a drug solution through said delivery lumen andout said exit port to a treatment site; a cylindrical ultrasoundtransducer coupled along said distal end portion of said inner core andlocated distal to said outer sheath; and a guidewire configured to beslidably received within said delivery lumen of said inner core foradvancement of said catheter to a treatment site.
 2. The catheter ofclaim 1, further comprising a soft tip assembly coupled to said distalend of said inner core.
 3. The catheter of claim 1, wherein said distalend portion of said catheter is shapeable for facilitating advancementof said catheter over said guidewire.
 4. The catheter of claim 1,further comprising a flexible joint proximal to said transducer, whereinsaid flexible joint has a reduced bending resistance for enhancingmaneuverability of said ultrasound catheter through said small vessel.5. The catheter of claim 1, further comprising at least one side holealong said soft tip assembly for providing a side port for deliveringsaid drug solution.
 6. The catheter of claim 1, wherein said distal tipis rounded in shape for minimizing damage along an inner wall of saidvessel.
 7. The catheter of claim 1, further comprising a stiffener ringcircumscribing said exit port at said distal tip, said stiffener ringbeing adapted to prevent said exit port from increasing in diameter. 8.A catheter, comprising: an outer sheath with an exterior surface,wherein a distal end portion of said outer sheath has an outer diameterof less than about 5 French for advancement through small vessels, saidouter sheath defining a delivery lumen extending longitudinallytherethrough; a guidewire configured to be slidably received within saiddelivery lumen; and an ultrasound transducer coupled to a distal endportion of said guidewire, wherein said guidewire is advanceable throughsaid delivery lumen for placement of said transducer in said distal endportion of said outer sheath.
 9. A method of treating a small vessel,comprising: providing a first guidewire, an elongate outer sheath, and asecond guidewire having an ultrasound radiating member disposed along adistal end; advancing said first guidewire though a patient'svasculature to a treatment site; advancing said elongate outer sheathover said first guidewire to said treatment site; removing said firstguidewire from said vasculature; advancing said second guidewire througha delivery lumen of said elongate outer sheath such that said ultrasoundradiating member is located along a distal end portion of said elongateouter sheath; and emitting ultrasound energy from said ultrasoundradiating member to said treatment site.
 10. The method of claim 9,further comprising delivering a drug solution through said deliverylumen to said treatment site.
 11. A catheter, comprising: an elongatetubular body with an exterior surface, wherein a distal end portion ofsaid tubular body has an outer diameter of less than about 5 French foradvancement through a small blood vessel, said tubular body defining adelivery lumen extending longitudinally therethrough and terminating inan exit port at a distal tip; a hypotube configured to be slidablyreceived within said delivery lumen; an ultrasound radiating membercoupled to a distal end portion of said hypotube, wherein said hypotubeis advanceable through said delivery lumen in said tubular body and outthrough said exit port for placement of said ultrasound radiating memberat a treatment site; and a pair of wires extending longitudinallythrough an inner lumen in said hypotube for providing an electricalsignal to said ultrasound radiating member.
 12. The catheter of claim11, further comprising a flexible nose coupled to a distal tip of saidultrasound radiating member.
 13. The catheter of claim 12, wherein saidflexible nose comprises a soft metal coil.
 14. The catheter of claim 11,further comprising a potting material for coupling said ultrasoundtransducer to a distal end portion of said hypotube.